From: Engineering considerations of iPSC-based personalized medicine
iPSC Preparation Stage | Techniques | Features | Outcomes | References |
---|---|---|---|---|
Reprogramming Techniques | Lentiviruses | iPSCs produced from adult fibroblast | Treatment with valproic acid increased cell proliferation | [21] |
Lentiviruses | iPSCs produced from mouse tail-tip fibroblast | Porphyra 334 increased the effectiveness of cell reprogramming | [22] | |
Sendai viruses | iPSCs produced from peripheral blood mononuclear cells | Heterozygous frameshift mutation in C19orf12 brought by the insertion | [23] | |
Episomal plasmids | iPSCs produced from mononuclear cells | No serious adverse events related to CYP-001 | [24] | |
Episomal plasmids | iPSCs produced from mouse embryonic fibroblast with small molecules | Tenfold increase in reprogramming efficiency | [25] | |
Episomal plasmids | iPSCs produced from a peri-infarct area | Endogenous brain repair, reduced inflammation and glial scar formation | [26] | |
Episomal plasmids | iPSCs produced from an amyotrophic lateral sclerosis patient’s cell | 5-hydroxymethyl cytosine levels increase the reprogramming | [27] | |
Circular DNA plasmids | iPSCs produced from B16F10 cells | Did not form teratomas, suppression of tumorigenic abilities | [28] | |
mRNA | iPSCs produced from neurons | Purified and differentiated into hair cell-like cells and neurons | [29] | |
mRNA | iPSCs produced from urine-derived cells | Generating feeder-free bulk hiPSC lines without genomic abnormalities | [30] | |
Small molecules | iPSCs produced from mouse embryonic fibroblasts | Facilitates both in vitro and in vivo alterations in cell fate | [31] | |
Small molecules | iPSCs produced from neural stem cells | Melatonin promoted N-iPSC proliferation | [32] | |
CRISPR-Cas9 | iPSCs produced from skin biopsies | Generate gene-edited hiPSCs from carrying a point mutation | [33] | |
Epigenetic modifications | iPSCs produced from mouse fibroblasts | Reconfigurations rapidly propel deterministic reprogramming toward naive pluripotency | [34] | |
C9ORF72-mutated | iPSCs produced from fibroblasts and peripheral blood cells | iPSCs and motor neurons derived from the two tissues showed identical properties and features | [35] | |
CtIP protein | iPSCs produced from mouse embryonic fibroblast | DNA repair fidelity to both human and mouse iPSCs | [36] | |
hiPSC3F-FIB or hiPSC4F-FIB | iPSCs produced from human fibroblasts and fetal neural stem cells | Does not alter subsequent differentiation into neural lineages | [37] | |
Integrated at the AAVS1 locus | iPSCs produced from neuron cells with neurogenin 2 transgene | In LOPAC, tau-lowering compounds has been identified | [38] | |
OSKM factors, absence of LIF | iPSCs produced from mouse embryonic fibroblasts | No tumor formation but formation of clear hyaline, hypertrophic cartilage | [39] | |
Six different reprogramming methods | iPSCs produced from fibroblasts and reprogramed by Lentivirus, Sendai, MiniCircle, Episomal, mRNA, and microRNA | Best results showed by Sendai-virus-based reprogramming | [40] | |
iPSC Expansion | Stirred based bioreactors | Expansion of macrophages generated from peripheral blood CD34 + cells-derived iPSCs | Highly pure CD45 + CD11b + CD14 + CD163 + cells, act like professional phagocytes | [41] |
Stirred based bioreactors | 1 ~ 4 × 107 iPSCs-derived macrophages can be harvested weekly | The ongoing, precise creation of iPSC-Mac populations | [42] | |
Vertical-wheel bioreactors | Expansion of human iPSCs as aggregates in single-use bioreactors | Expand iPSCs to expand cells up to 2.3 × 106 (Maximum cell density) | [43] | |
Vertical-wheel bioreactors | With a cumulative cell expansion of 1.06 × tenfold in 28 days, the expansion is 30 times in 6 days | Rapid generation of high-quality hiPSCs | [44] | |
Vertical-wheel bioreactors with GelMA microcarriers | 8-day cell growth that increased 16-fold, differentiation, and immune modulation capacity | Robust, scalable, and cost-effective with translational potential | [45] | |
Spinner flask bioreactors | Primary macrophages with cytokine release, phagocytosis, and chemotaxis | Synthesis of genetically altered, iPSC-derived macrophages on a large scale | [46] | |
Hydrogel-based 3D culture | Promotes endothelial-network formation and identifies angiogenesis inhibitors | Superior sensitivity and reproducibility over Matrigel | [47] | |
Hydrogel-based 3D culture | Fibroblasts formed tiny clusters, spheroids, short segments and on day 20, lengthy segments | The production of closed, inexpensive devices and iPSCs is more rapid, reliable, and scalable | [48] | |
Transwell-based 3D culture | In vivo, ex vivo, and in vitro nephrogenic potential, able to produce metabolites that resemble urine | A platform for renal disorders, drug discovery, and human nephrogenesis | [49] | |
Multi-culture flasks | Glycogen synthase kinase-3b suppression, CHIR99021 causes a massive proliferation of hiPSC-CMs in vitro (100- to 250-fold) | Expanding hiPSCs for use in tissue engineering and drug screening in a large-scale | [50] | |
Chemically defined culture medium | Human skin fibroblasts or peripheral blood mononuclear cells are used to create iPSCs | Differentiation into three embryonic germ layers | [51] | |
Chemically defined culture medium | hiPSCs with increased metabolic activity derived from blastocysts or somatic cells | GMP-friendly methods for the manufacturing and processing of therapeutic hiPSC | [52] | |
Plate shaker based liquid handler | Cell seeding, splitting, expansion, differentiation image-based multiparametric screening | NPC's neuronal differentiation in 3D midbrain organoids and 2D culture | [53] | |
Culture dishes coated with polymer | Create particles with zwitterionic polymer that resemble hyaline cartilaginous tissue and type II collagenopathy | Mass production of chondrocytes and cartilaginous tissues used for drug screening | [54] | |
Establishment of iPSC Line | Mutagenized iPSC line | CRISPR/Cas9-dependent reprogramming iPSCs | Development of loss-of-function disease models | [55] |
Heterozygous COL1A1 mutation iPSC lines | Karyotype expressed pluripotency markers | Osteogenesis imperfecta disease mechanisms | [56] | |
Homozygous/heterozygous iPSC lines | CRISPR-Cas9 dependent reprogramming | Generation of two isogenic iPSC lines | [57] | |
KCNA2 mutation iPSC lines | KCNA2 point mutation for produce induces pluripotent stem cells | Expression of pluripotency markers, differentiation into three germ layers | [58] | |
Footprint-free iPSC lines | Whole-genome sequencing-based annotated iPSCs lines | Personal Genome Project Canada for personalized iPSC line | [59] | |
cGMP-manufactured hiPSC lines | Can produce retinal cells | A human iPSC line that has been used to create transplantable photoreceptors | [60] | |
CD34 + hematopoietic cells iPSC lines | CD34 + hematopoietic stem cells from peripheral blood | The production and characterization of three hiPSC lines compatible with GMP | [61] | |
Process Automation | Fully automated | Microcolonies throughout a 7-day period, sensitivity of 88%, and 98% detection specificity | label-free sensing and mother colony maintenance | [62] |
Fully automated | Retinal pigment epithelial cells are produced using TECAN Fluent automated cell culture | A commercially available platform called end-to-end workflow | [63] | |
Automated reprogramming process | Platform for differentiated cells that uses robotics and human involvement | Population-scale personalized iPSC line | [64] | |
Automated reprogramming, isolation, and expansion process | Expression of the TRA-1–60 marker for pluripotent stem cells | Commercialized iPSCs line establishment | [65] | |
Automated cell culture process | The cell yields, aggregation rates, and expression were higher in non-centrifugation populations | Successfully transferred to independent laboratories | [66] | |
Automated cell culture process | Differentiated into dopaminergic neurons, pancreatic cells, and pancreatic hormones | Differentiated into three germ layers | [15] | |
Automated quality assessment process | A k-NN classifier with three potential classes has the best accuracy (62,4%) for classification | Automatic evaluation of iPSC colony image quality | [67] | |
Biologically inspired AI-based automated process | More adaptable and capable of resolving a wide variety of optimization issues | A necessary simulation is introduced along with the proper model fitting technique | [68] |